Mucopolysaccharidosis IIPhase 2/3NCT00069641
Iduronate-2-sulfatase Enzyme Replacement Therapy in Mucopolysaccharidosis II (MPS II)
A Phase 2/3 study testing Iduronate-2-sulfatase enzyme replacement therapy in people with Mucopolysaccharidosis II, run by Shire at 9 sites in 4 countries.
Trial summary
The purpose of this study is to determine whether the administration of iduronate-2-sulfatase enzyme in a weekly or every other week therapy frequency is safe and efficacious in patients with MPS II. Read more about this study
- Who is it for?
- Ages 5 to 25 years, men only
- Conditions the study is for
- Mucopolysaccharidosis II
- What is being tested?
- Iduronate-2-sulfatase enzyme replacement therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 18 Sep 2003to 16 Mar 2005
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 25 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- To be eligible to participate in this study, patients must meet the following inclusion criteria prior to enrollment:
- The diagnosis of MPS II will be determined by the investigator based upon both clinical and biochemical criteria.
- All patients must have at least one of the following Clinical Criteria considered by the investigator to be MPS II-related:
- Hepatosplenomegaly
- Radiographic evidence of dysostosis multiplex
- Valvular heart disease
Show all 14Show fewer
- Evidence of obstructive pulmonary disease
- In addition, patients must have the following Biochemical Criteria:
- Documented deficiency in iduronate-2-sulfastase enzyme activity of less than or equal to 10% of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
- A normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
- Must be male, 5 to 25 years of age.
- Forced vital capacity of <80% of predicted obtained at the baseline evaluation of this study.
- Must be able to adequately perform the testing required in this study, including reproducible pulmonary function testing by spirometry, as judged by the investigator.
- Patient, patient's parent(s), or legally authorized guardian must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient.
Who cannot join
- Patients meeting any of the following criteria are not eligible for participation in this study:
- Patient has received treatment with another investigational therapy within the past 60 days.
- Patient, patient's parent(s), or patient's legal guardian is unable to understand the nature, scope, and possible consequences of the study.
- Patient is unable to comply with the protocol (e.g., due to a medical condition such as cervical cord compression or uncooperative attitude) or is unlikely to complete the study, as determined by the investigator.
- Patient has a tracheostomy.
- Patient has received a bone marrow or cord blood transplant.
- Patient with known hypersensitivity to any of the components of iduronate-2-sulfatase.
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
United States4 sites
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Texas Children's Hospital, Baylor College of Medicine
Houston, Texas, 77030
Children's Hospital Oakland
Oakland, California, 94609
St. Louis Children's Hospital, Washington University
St Louis, Missouri, 63110
United Kingdom3 sites
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Great Ormond Street Hospital for Sick Children
London, England, WC1N3JH
Royal Manchester Children's Hospital
Manchester, England, M27 4HA
Germany1 site
Children's Hospital, Johannes-Gutenburg Universitaet Mainz
Mainz
About this study
Official title: A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Weekly and Every Other Week Dosing Regimens of Iduronate-2-Sulfatase Enzyme Replacement Therapy in Patients With MPS II
The purpose of this study is to determine whether the administration of iduronate-2-sulfatase enzyme in a weekly or every other week therapy frequency is safe and efficacious in patients with MPS II.
Read the detailed description
MPS II is a rare, X-linked, lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase. Because of this deficiency, glycosaminoglycans (GAG) accumulate in multiple tissues and organs, resulting in progressive cellular and organ system dysfunction. The purpose of this study is to determine if one year of therapy with iduronate-2-sulfatase enzyme replacement therapy, at a dose of 0.5mg/kg, weekly or every other week, is safe, and results in clinically meaningful improvement in multiple organ function, compared with a placebo group. Upon completion of the study, patients will be eligible to enroll in an open-label maintenance study.
- Conditions
- Mucopolysaccharidosis II
- Being tested
- Iduronate-2-sulfatase enzyme replacement therapy, Placebo
- Keywords
- Mucopolysaccharidosis II, MPS II, Hunter Syndrome, iduronate-2-sulfatase, I2S, Iduronate-2-sulfatase deficiency
- Medical subject headings
- Mucopolysaccharidosis II, Sudden Infant Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iduronate-2-sulfatase enzyme replacement therapyBiological
Also called Elaprase
Patients will receive weekly infusions of idursulfase at a dose of 0.5 mg/kg.
iduronate-2-sulfatase enzyme replacement therapyBiological
Also called Elaprase
Patients will receive every other week infusions of idursulfase at a dose of 0.5 mg/kg.
PlaceboBiological
Patients will receive weekly infusions of placebo.
| Study group | Role | What they receive |
|---|---|---|
| Idursulfase weekly (0.5 mg/kg) | Experimental | Not described Receives: Biological: Iduronate-2-sulfatase enzyme replacement therapy |
| Idursulfase every other week (0.5 mg/kg) | Experimental | Not described Receives: Biological: iduronate-2-sulfatase enzyme replacement therapy |
| Placebo | Placebo comparator | Not described Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53
The 2-component composite variable consists of the sum of the ranked changes from baseline to Week 53 for percent predicted Forced Vital Capacity (FVC) and 6-Minute Walking Test (6MWT) total distance walked. For the 2 treatment groups being compared, ranking occurred within the comparison treatment groups combined (idursulfase weekly and placebo treatment groups). These comparison groups were pooled and ranked for each component separately. Within each component (% predicted FVC, 6MWT), the change from baseline was then ranked. The lowest change value was assigned a rank of 1, the next lowest a rank of 2, etc. The composite score for each participant was the sum of the 2 ranked scores corresponding to the 2 individual components (% predicted FVC and 6MWT) for each participant. Thus, the greater the composite score (greater the sum of the ranks of the changes from baseline, where the lowest change was ranked as 1), the greater the improvement.
Measured: Baseline, Week 53
Secondary outcomes (6)
Change From Baseline in Mean Global Joint Range of Motion (JROM) Score at Week 53
Change was calculated at Week 53 from baseline. Global JROM (% of normal range of motion) is the average of 11 ratios multiplied by 100. Ratios are Left/Right means of passive range of motion in Shoulder (Flexion/Extension, Abduction, Internal/External Rotation), Elbow (Flexion/Extension), Wrist (Flexion/Extension), Index Finger (Flexion/Extension [Combined Metacarpophalangeal joint (MCP), Proximal interphalangeal joint (PIP), Distal interphalangeal joint (DIP) motion]), Hip (Flexion/Extension, Abduction, Internal/External Rotation), Knee (Flexion/Extension), and Ankle (Dorsiflexion) divided by the normal range (American Academy of Orthopedic Surgeons and American Medical Association).
Measured: Baseline, Week 53
Mean Combined Liver and Spleen Volume at Baseline
Liver and Spleen volume was determined by Magnetic Resonance Imaging (MRI).
Measured: Baseline
Percent Change From Baseline in Mean Combined Liver and Spleen Volume at Week 53
Liver and Spleen volume was determined by Magnetic Resonance Imaging (MRI). Change was calculated at Week 53 from baseline.
Measured: Baseline, Week 53
Change From Baseline in Mean Normalized Urine Glycosaminoglycan (GAG) Levels at Week 53
Mean normalized urine GAG was analyzed using urine testing. Change was calculated at Week 53 from baseline. The urine GAG levels were normalized to urine creatinine and were reported as microgram GAG per milligram creatinine (mcg GAG/mg creatinine).
Measured: Baseline, Week 53
Mean Cardiac Left Ventricular Mass Index (LVMI) at Baseline
Cardiac LVMI was determined by echocardiography. LVMI is the left ventricular mass (LVM, in grams [g]) indexed to body surface area (BSA), in square meter [m^2]. LVMI (in gram per square meter [g/m^2]) = LVM divided by BSA.
Measured: Baseline
Percent Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 53
Cardiac LVMI was determined by echocardiography. Change was calculated at Week 53 from baseline. LVMI is the LVM, in grams indexed to BSA, in square meter [m^2]. LVMI in g/m^2 = LVM divided by BSA.
Measured: Baseline, Week 53
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2003 (estimated)
- Study start18 Sep 2003
- Primary completion16 Mar 2005
- Study completion16 Mar 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mucopolysaccharidosis IIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00069641
- Sponsor's protocol ID
- TKT024
- Status last verified
- May 2021
- First submitted
- 29 Sep 2003
- Last updated
- 10 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.
PubMed 33874971Raluy-Callado M, Chen WH, Whiteman DA, Fang J, Wiklund I. The impact of Hunter syndrome (mucopolysaccharidosis type II) on health-related quality of life. Orphanet J Rare Dis. 2013 Jul 10;8:101. doi: 10.1186/1750-1172-8-101.
PubMed 23837440
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Weekly and Every Other Week Dosing Regimens of Iduronate-2-Sulfatase Enzyme Replacement Therapy in Patients With MPS II
- ClinicalTrials.gov ID
- NCT00069641
- Acronym / sponsor ID
- TKT024
- Conditions
- Mucopolysaccharidosis II
- Keywords
- Mucopolysaccharidosis II, MPS II, Hunter Syndrome, iduronate-2-sulfatase, I2S, Iduronate-2-sulfatase deficiency
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 18 Sep 2003 (actual)
- Primary completion
- 16 Mar 2005 (actual)
- Study completion
- 16 Mar 2005 (actual)
- First posted
- 1 Oct 2003 (estimated)
- Results
- Posted 13 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the administration of iduronate-2-sulfatase enzyme in a weekly or every other week therapy frequency is safe and efficacious in patients with MPS II.
Detailed description
MPS II is a rare, X-linked, lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase. Because of this deficiency, glycosaminoglycans (GAG) accumulate in multiple tissues and organs, resulting in progressive cellular and organ system dysfunction. The purpose of this study is to determine if one year of therapy with iduronate-2-sulfatase enzyme replacement therapy, at a dose of 0.5mg/kg, weekly or every other week, is safe, and results in clinically meaningful improvement in multiple organ function, compared with a placebo group. Upon completion of the study, patients will be eligible to enroll in an open-label maintenance study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Idursulfase weekly (0.5 mg/kg) | Experimental | Biological: Iduronate-2-sulfatase enzyme replacement therapy |
| Idursulfase every other week (0.5 mg/kg) | Experimental | Biological: iduronate-2-sulfatase enzyme replacement therapy |
| Placebo | Placebo comparator | Biological: Placebo |
Who may qualify
- Ages
- 5 to 25 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- To be eligible to participate in this study, patients must meet the following inclusion criteria prior to enrollment:
- The diagnosis of MPS II will be determined by the investigator based upon both clinical and biochemical criteria.
- All patients must have at least one of the following Clinical Criteria considered by the investigator to be MPS II-related:
- In addition, patients must have the following Biochemical Criteria:
- Must be male, 5 to 25 years of age.
Key exclusion criteria (7 listed)
- Patients meeting any of the following criteria are not eligible for participation in this study:
- Patient has received treatment with another investigational therapy within the past 60 days.
- Patient, patient's parent(s), or patient's legal guardian is unable to understand the nature, scope, and possible consequences of the study.
- Patient is unable to comply with the protocol (e.g., due to a medical condition such as cervical cord compression or uncooperative attitude) or is unlikely to complete the study, as determined by the investigator.
- Patient has a tracheostomy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Iduronate-2-sulfatase enzyme replacement therapyAlso: ElaprasePatients will receive weekly infusions of idursulfase at a dose of 0.5 mg/kg. | Biological | Idursulfase weekly (0.5 mg/kg) |
| iduronate-2-sulfatase enzyme replacement therapyAlso: ElaprasePatients will receive every other week infusions of idursulfase at a dose of 0.5 mg/kg. | Biological | Idursulfase every other week (0.5 mg/kg) |
| PlaceboPatients will receive weekly infusions of placebo. | Biological | Placebo |
Primary outcome
Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53
Time frame: Baseline, Week 53
The 2-component composite variable consists of the sum of the ranked changes from baseline to Week 53 for percent predicted Forced Vital Capacity (FVC) and 6-Minute Walking Test (6MWT) total distance walked. For the 2 treatment groups being compared, ranking occurred within the comparison treatment groups combined (idursulfase weekly and placebo treatment groups). These comparison groups were pooled and ranked for each component separately. Within each component (% predicted FVC, 6MWT), the change from baseline was then ranked. The lowest change value was assigned a rank of 1, the next lowest a rank of 2, etc. The composite score for each participant was the sum of the 2 ranked scores corresponding to the 2 individual components (% predicted FVC and 6MWT) for each participant. Thus, the greater the composite score (greater the sum of the ranks of the changes from baseline, where the lowest change was ranked as 1), the greater the improvement.
6 secondary outcomes
Change From Baseline in Mean Global Joint Range of Motion (JROM) Score at Week 53
Time frame: Baseline, Week 53
Mean Combined Liver and Spleen Volume at Baseline
Time frame: Baseline
Percent Change From Baseline in Mean Combined Liver and Spleen Volume at Week 53
Time frame: Baseline, Week 53
Change From Baseline in Mean Normalized Urine Glycosaminoglycan (GAG) Levels at Week 53
Time frame: Baseline, Week 53
Mean Cardiac Left Ventricular Mass Index (LVMI) at Baseline
Time frame: Baseline
Percent Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 53
Time frame: Baseline, Week 53
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33874971Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.
- Derived from this study: PubMed 23837440Raluy-Callado M, Chen WH, Whiteman DA, Fang J, Wiklund I. The impact of Hunter syndrome (mucopolysaccharidosis type II) on health-related quality of life. Orphanet J Rare Dis. 2013 Jul 10;8:101. doi: 10.1186/1750-1172-8-101.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Iduronate-2-sulfatase enzyme replacement therapy in people with Mucopolysaccharidosis II, run by Shire at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, United Kingdom, Brazil, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53 (time frame: Baseline, Week 53). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00069641, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.